What Mistakes Can Occur when DNA is Replicated

Genetic Mutations What mistakes can occur when DNA is replicated? Why? The genes encoded in your DNA result in the production of proteins that perform specific functions within your cells. Various environmental factors and spontaneous events can lead to changes in genes. These changes, called mutations, can lead to alterations in the structure and activity of the proteins your cells use in their daily activities. In other words, changes to your genotype can result in changes to your phenotype. We all have mutations in most of our body cells—yet we are, for the most part, normal and functional human beings. How can that be? Model 1 – Gene Mutations Sequence 1 (normal) DNA sequence … T A C G T A G T C A C C T A A T G G A T C… mRNA sequence A U G C A U C A G U G G A U U A C C U A G Amino acid sequence Met His Gln Trp DNA sequence mRNA sequence Amino acid sequence mRNA sequence Amino acid sequence mRNA sequence Amino acid sequence stop A U G C A U C A G U C G A U U A C C U A G Met His Gln Ser Ile Thr stop frameshift mutation … T A C G T A T G T C A C C T A A T G G A T C… A U G C A U A C A G U G G A U U A C C U A G… Met His Thr Sequence 4 (deletion) DNA sequence Thr … T A C G T A G T C A G C T A A T G G A T C… Sequence 3 (insertion) DNA sequence Ile C Sequence 2 (substitution) Val Asp Tyr Leu... A … T A C G T A G T C C C T A A T G G A T C… A U G C A U C A G G G A U U A C C U A G… Met His Gln Gly Leu Pro… frameshift mutation 1. How many nucleotides are present in the “normal” DNA sequence in Model 1? 21 nucleotides 2. How many codons are contained in the mRNA that is produced by the “normal” DNA in Model 1? 7 codons (triplets) 3. How many amino acids will be in the polypeptide produced by the normal DNA/mRNA sequence? 7 amino acids 1 4. What is the amino acid sequence of the polypeptide produced by the “normal” DNA sequence in Model 1? AUGCAUCAGUGGAUUACCUAG 5. Consider DNA sequence 2 in Model 1. The mutation in that sequence is a substitution mutation. a. Compare sequence 2 with sequence 1 and describe the mutation that has occurred. UGG- UCG Trp-- Ser b. What is the effect of this substitution mutation on the amino acid sequence? not the same length different amino acids 6. Consider DNA sequence 3 in Model 1. The mutation in that sequence is an insertion mutation. a. Compare sequence 3 with sequence 1 and describe the mutation that has occurred. b. What is the effect of the insertion mutation on the amino acid sequence as compared to the “normal” amino acid sequence in Model 1? An additional nucleotide is inserted in the normal sequence, which lengthens the sequence 7. Consider DNA sequence 4 in Model 1. The mutation in that sequence is a deletion mutation. a. Compare sequence 4 with sequence 1 and describe the mutation that has occurred. not the same length different amino acids b. What is the effect of the deletion mutation on the amino acid sequence as it is compared to the “normal” amino acid sequence in Model 1? missing U not the same length different amino acid 8. In your group, use grammatically correct sentences to define each of the following mutations. Substitution mutation— 2 changes a nucleotide Insertion mutation— adds a nucleotide Deletion mutation— removes a nucleotide 9. Considering your knowledge of codons and how they code for an amino acid, would all substitution mutations lead to a change in the amino acid sequence? Explain your reasoning. No; the silent substitution didn't change. The codon changed, but the amino acid didn't. 10. Would all insertion or deletion mutations lead to a change in the amino acid sequence? Explain your reasoning. Yes because any new nucleotide that is inserted / deleted shifts the nucleotides, changing the letters of multiple codons. 11. What could potentially cause more damage (or a greater benefit) to an organism, a substitution mutation or an insertion mutation? Explain your reasoning. Insertion because it has the potential to change a majority of the normal amino acid sequence, as the reading frame shifts. 12. What could potentially cause more damage (or a greater benefit) to an organism, a deletion mutation at the beginning of a DNA sequence or at the end of a DNA sequence? The beginning because the codons following would all change, whereas a deletion mutation at the end would not affect the codons that were present before. 13. All of the DNA and mRNA sequences in Model 1 have ellipses (…) on one or both ends of the sequences shown. Propose an explanation for this use of this symbol in that context. the sequence is too long 14. The amino acids produced from sequence 1 and sequence 2 in Model 1 do not have ellipses on the end of them, however the amino acids produced from sequence 3 and sequence 4 do have ellipses. Propose an explanation for the use or absence of the ellipses on these sequences. the sequence changed length 3 Model 2 – Comparing Substitution Mutations Original DNA: mRNA: Amino acid: Mutation A: mRNA: Amino acid: Mutation B: mRNA: Amino acid: Mutation C: mRNA: Amino acid: … T A C C C T A G G A A T A T C A A A… A U G G G A U C C U U A U A G U U U… Met Gly Ser Leu stop … T A C C C T A G G A A A A T C A A A…. A U G G G A U C C U U U U A G U U U… Met Gly Ser Phe stop … T A C C C T A G C A A T A T C A A A…. A U G G G A U C G U U A U A G U U U… Met Gly Ser Leu stop … T A C A C T A G G A A T A T C A A A… A U G U G A U C C U U A U A G U U U… Met stop Mutation D: T A G C C T A G G A A T A T C A A A… mRNA: A U C G G A U C C U U A U A G U U U… Amino acid: No protein will be translated because there is no start codon. 15. For each of the mutations A – D in Model 2, circle the substitution that occurred by comparing the mutated DNA with the original DNA. 16. As a group, describe the range of changes in the amino acid sequence that can result from this type of mutation. nothing could change (mutation B) or all could change (mutation D) 4 17. Gene mutations can be positive, negative or neutral. Suppose that the normal gene in Model 2 produced a polypeptide that was necessary for cellular respiration. a. Choose a mutation from those in Model 2 that would be neutral for a cell. Explain your reasoning by relating the mutation to the cellular respiration process. mutation b b. Choose a mutation from those in Model 2 that might be positive for a cell. Explain your reasoning by relating the mutation to the cellular respiration process. mutation a c. Choose a mutation from those in Model 2 that might be negative for a cell. Explain your reasoning by relating the mutation to the cellular respiration process. mutation c Read This! Mutations are the source of all new alleles in nature. Variations in alleles lead to variations in organisms within a population. Positive mutations lead to the organism having a better chance of survival, which means the mutation may be passed on to the offspring. Negative mutations may lead to an early death— probably before the organism can produce offspring. Therefore, changes in alleles from one generation to another form the basis of evolution. 18. Which types of mutations, positive, negative or neutral, are most likely to be seen in offspring several generations after the mutation occurred? Explain your reasoning. positive 19. Consider the following scenarios. State whether the mutation is likely to be passed on to the offspring of the organism. Explain your reasoning. a. A single bacteria cell contains a positive mutation in its DNA. yes b. A skin cell on a cat contains a positive mutation in its DNA. only if reproductive cells mutated too c. A sperm cell in a whale contains a positive mutation in its DNA. yes 5 20. All cells have DNA errors due to the mistakes that occur each time DNA is replicated prior to cell division. There are proofreading enzymes in cells that correct many of these mistakes, but on average, 3 – 5 errors are found in DNA after each replication. a. If each cell has multiple mutations, why do most of us have normally-functioning tissues and organs? you have so many cells that small mutations are unlikely to harm you b. Why is only a tiny subset of these mutations passed on to our children? only mutations that effect the reproductive cells are passed on, this is because of sexual reproduction 6 Extension Questions 21. A gene mutation is a change in the sequence of nucleotides that occurs during cell replication (mitosis and meiosis) within a single coding section of DNA. Mistakes can also occur in the transcription of mRNA or the translation of a polypeptide. However, these changes are not considered to be mutations, because they are not permanent changes to the cell. Explain why “mistakes” in transcription or translation are not as serious as mutations in a gene. genes code for your whole body mRNA only gives instructions to your cells after they are formed. 22. Insertion and deletion mutations are said to cause shifts in the “reading frame” (the sets of three nucleotides) of the mRNA. Substitution mutations do not cause these so-called frameshifts. Explain why insertions and deletions are called frameshift mutations, using the terms reading frame, codons, and amino acids in your answer. changing the total number of nucleotides shifts the reading frame and will make a totally different set of amino acids. 7